AUTHOR=Zeng Weilin , Zhao Hui , Zhao Wei , Yang Qi , Li Xinxin , Li Xiaosong , Duan Mengxi , Wang Xun , Li Cuiying , Xiang Zheng , Chen Xi , Cui Liwang , Yang Zhaoqing 

TITLE=Molecular Surveillance and Ex Vivo Drug Susceptibilities of Plasmodium vivax Isolates From the China–Myanmar Border

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.738075

DOI=10.3389/fcimb.2021.738075

ISSN=2235-2988

ABSTRACT=<p>Drug resistance in <italic>Plasmodium vivax</italic> may pose a challenge to malaria elimination. Previous studies have found that <italic>P. vivax</italic> has a decreased sensitivity to antimalarial drugs in some areas of the Greater Mekong Sub-region. This study aims to investigate the <italic>ex vivo</italic> drug susceptibilities of <italic>P</italic>. <italic>vivax</italic> isolates from the China–Myanmar border and genetic variations of resistance-related genes. A total of 46 P. <italic>vivax</italic> clinical isolates were assessed for <italic>ex vivo</italic> susceptibility to seven antimalarial drugs using the schizont maturation assay. The medians of IC<sub>50</sub> (half-maximum inhibitory concentrations) for chloroquine, artesunate, and dihydroartemisinin from 46 parasite isolates were 96.48, 1.95, and 1.63 nM, respectively, while the medians of IC<sub>50</sub> values for piperaquine, pyronaridine, mefloquine, and quinine from 39 parasite isolates were 19.60, 15.53, 16.38, and 26.04 nM, respectively. Sequence polymorphisms in <italic>pvmdr1</italic> (<italic>P</italic>. <italic>vivax</italic> multidrug resistance-1), <italic>pvmrp1</italic> (<italic>P</italic>. <italic>vivax</italic> multidrug resistance protein 1), <italic>pvdhfr</italic> (<italic>P</italic>. <italic>vivax</italic> dihydrofolate reductase), and <italic>pvdhps</italic> (<italic>P</italic>. <italic>vivax</italic> dihydropteroate synthase) were determined by PCR and sequencing. <italic>Pvmdr1</italic> had 13 non-synonymous substitutions, of which, T908S and T958M were fixed, G698S (97.8%) and F1076L (93.5%) were highly prevalent, and other substitutions had relatively low prevalences. <italic>Pvmrp1</italic> had three non-synonymous substitutions, with Y1393D being fixed, G1419A approaching fixation (97.8%), and V1478I being rare (2.2%). Several <italic>pvdhfr</italic> and <italic>pvdhps</italic> mutations were relatively frequent in the studied parasite population. The <italic>pvmdr1</italic> G698S substitution was associated with a reduced sensitivity to chloroquine, artesunate, and dihydroartemisinin. This study suggests the possible emergence of <italic>P</italic>. <italic>vivax</italic> isolates resistant to certain antimalarial drugs at the China–Myanmar border, which demands continuous surveillance for drug resistance.</p>